Equine & Livestock Product & Promotions Guide

MICROBIOLOGY Based on data provided for the approval of Draxxin ® (tulathromycin injection, NADA 141-244), tulathromycin has demonstrated in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, four pathogens associated with BRD. TARGET ANIMAL SAFETY Thirty-two (16 male and 16 female) growing cattle were enrolled in a margin of safety study. Calves were injected subcutaneously with either saline, DRAXXIN KP at the label dose 2.5 mg tulathromycin/3 mg ketoprofen/kg BW, DRAXXIN KP at 3 times the label dose, or DRAXXIN KP at 5 times the label dose. Calves received three doses at a 14-day interval between doses. Daily clinical observations were conducted by a veterinarian as well as daily general health observations and injection site evaluations. Samples were collected for urinalysis, fecal occult blood, hematology, serum chemistry and coagulation and for pharmacokinetics. At the conclusion of the study, all animals were euthanized and necropsied for gross pathology and histopathology evaluation. Injection site lesion volumes for the first injection site was calculated. Injection site reactions were noted in all DRAXXIN KP-treated animals and the size and incidence of injection site lesions were greater in the 3X and 5X treatment groups. Test article-related differences in serum chemistry parameters were lower alkaline phosphatase in the 5X group; lower albumin in the 3X and 5X groups; lower total protein (TP) and serum calcium in the 1X, 3X and 5X groups; and higher creatine kinase (CK) in the 1X, 3X, and 5X groups. The changes for serum calcium and albumin were considered clinically insignificant because all values were within the normal reference range on the days with statistical differences. The changes for TP were considered secondary to the differences in albumin and clinically insignificant because the albumin changes were considered clinically insignificant. In addition, the only TP values that were outside of the normal reference range were only 0.1 g/dL below the normal reference range. The differences in neutrophil values might be secondary to test article- associated injection site inflammation and the differences in CK values are directly associated with injection site reactions.There were non-quantifiable ketoprofen plasma concentrations prior to the second and third doses, while there was a modest accumulation for tulathromycin (mean ≤16.5%) with the 14-day dosing interval. There was dose proportional increase in tulathromycin AUC0-t(last) with an increase in dose, while there was slightly greater than dose proportional increase in ketoprofen AUC0-t(last). A single calf in Group T04 had test article-associated positive fecal occult blood samples on Days 15 and 29. Microscopic mucosal erosions of the pylorus of the abomasum were present in the 3X (2/8) and 5X (1/8) groups and was considered test article-related. Renal interstitial inflammation and minimal multifocal degeneration and regeneration occurred at similar incidence and severity in treated and control calves. Subcutaneous injection of cattle with tulathromycin- ketoprofen at the label dose was well tolerated. EFFECTIVENESS A multi-location field study was conducted to evaluate the effectiveness of Draxxin ® KP for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of pyrexia associated with BRD. A total of 819 cattle with clinical signs of BRD (moderate depression and respiratory distress, and a rectal temperature ≥104.5 °F) were enrolled and treated with either saline (0.025 mL/kg BW), tulathromycin (2.5 mg/kg BW) or Draxxin ® KP (2.5 mg tulathromycin/kg BW and 3 mg ketoprofen/kg BW) administered by subcutaneous injection. Rectal temperatures were measured six hours later and animals were observed for clinical signs of BRD through 14 days post-treatment. An animal was classified as a treatment success for treatment of BRD if it was not classified as a failure prior to Day 14, and had normal or mild depression and respiratory distress scores and a rectal temperature <104.5 °F on Day 14. An animal was classified as a treatment success for control of pyrexia associated with BRD if it displayed a ≥2 °F reduction in rectal temperature at 6-hours post-treatment compared to pre-treatment. The Draxxin ® KP-treated group had a significantly different (P=0.0020) and numerically higher success rate (76.2%) for the treatment of BRD compared to the saline-treated group (31.6%), and the success rate in the Draxxin ® KP-treated group was statistically non-inferior to that in the group receiving tulathromycin alone. The success rate (back-transformed estimate) for pyrexia associated with BRD in the Draxxin ® KP-treated group was significantly different (P=0.0010) and numerically higher (83.8%) at 6 hours post-treatment than the success rate in the saline-treated group (2.4%). The success rate (back-transformed estimate) for pyrexia associated with BRD in the Draxxin ® KP-treated group was significantly different (P=0.0032) and numerically higher (83.9%) at 6 hours post-treatment than the success rate in the tulathromycin-treated group (5.4%). A sufficient number of Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis were isolated from cattle in the study to demonstrate that these BRD pathogens were contributing to the observed disease. HOW SUPPLIED DRAXXIN KP Injection is available in the following package sizes: 50 mL vial 100 mL vial 250 mL vial 500 mL vial STORAGE CONDITIONS Store at or below 25°C (77°F), with excursions up to 40°C (104°F). Protect from freezing. APPROVED BY FDA under NADA # 141-543 Distributed by: Zoetis Inc. Kalamazoo, MI 49007 Product of Spain May 2021 40028876/40028876/40028872/40028868A&P

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